Solvent detergent emulsions having antiviral activity

Abstract

Methods and pharmaceutical compositions for inactivating an envelope virus using an oil-in-water emulsion including an oil, a surfactant, and an organic phosphate-based solvent are disclosed. These methods can be used to inactivate a wide variety of envelope viruses, such as HIV.

What is claimed is: 
     
       1. A method of inactivating an envelope virus comprising the steps of providing a storage stable, virus inactivating, oil-in-water emulsion composed of droplets having a mean particle size in the range of about 0.5 to 1.5 microns in the form of a discontinuous oil phase distributed in an aqueous phase with a non-ionic stabilizer selected from the group consisting of Tween 20, Tween 80 and Triton X-100, said nonionic stabilizer being present in between about 0.2-2% of said composition, said aqueous phase being in the form of a pharmaceutically acceptable vehicle and forming about 80-98% of said composition, said oil phase containing a carrier oil and tributyl phosphate, said tributyl phosphate forming about 0.2-2% of said composition; and   contacting said virus with said emulsion such that said virus is inactivated.   
     
     
       2. The method of claim 1 wherein said surfactant is Triton X-100. 
     
     
       3. The method of claim 1 wherein said carrier oil is selected from the group consisting of soybean oil, avocado oil, squalane oil, squalene oil, olive oil, canola oil, corn oil, rapeseed oil, safflower oil, sunflower oil, fish oils, flavor oils, water insoluble vitamins and mixtures thereof. 
     
     
       4. The method of claim 3 wherein said carrier oil comprises soybean oil. 
     
     
       5. The method of claim 1, wherein said envelope virus is selected from the group consisting of Herpesviridae, Togaviridae, Flaviviridae, Coronaviridae, Rhabdoviridae, Filoviridae, Paramyxoviridae, Orthomyxoviridae, Arenaviridae, Retroviridae, and Hepadnavirida. 
     
     
       6. The method of claim 1, wherein the virus is HIV. 
     
     
       7. The method of claim 1, wherein the virus is selected from the group consisting of HSV-1, HSV-2, CMV and VSV. 
     
     
       8. A pharmaceutical composition for inactivating a virus, said composition comprising in a storage stable, virus inactivating, oil-in-water emulsion composed of droplets having a mean particle size in the range of about 0.5 to 1.5 microns in the form of an oil phase distributed in an aqueous phase with a nonionic stabilizer selected from the group consisting of Tween 20, Tween 80 and Triton X-100, said nonionic stabilizer being present in between about 0.2-2% of said composition, said aqueous phase being in the form of a pharmaceutically acceptable vehicle and forming about 80-98% of said composition, said oil phase containing a carrier oil and tributyl phosphate, said tributyl phosphate forming about 0.2-2% of said composition. 
     
     
       9. The pharmaceutical composition of claim 12 wherein said non-ionic stabilizer comprises Triton X-100. 
     
     
       10. The composition of claim 9 wherein said surfactant is Triton X-100. 
     
     
       11. The composition of claim 8 wherein said carrier oil consists essentially of a vegetable oil. 
     
     
       12. The composition of claim 11 wherein said vegetable oil comprises soybean oil. 
     
     
       13. A method of inhibiting viral infection caused by an envelope virus in a subject, said method comprising the steps of providing a storage stable, virus inactivating, oil-in-water emulsion composed of droplets having a mean particle size in the range of about 0.5 to 1.5 microns in the form of an oil phase distributed in an aqueous phase with a non-ionic selected from the group consisting of Tween 20, Tween 80 and Triton X-100, said nonionic stabilizer being present in between about 0.2-2% of said composition, said aqueous phase being in the form of a pharmaceutically acceptable vehicle and forming about 80-98% of said composition, said oil phase containing a carrier oil and tributyl phosphate, said tributyl phosphate forming about 0.2-2% of said composition; and   administering said emulsion to said subject such that said emulsion contacts said envelope virus, such that viral infection is inhibited.   
     
     
       14. The method of claim 13 wherein said administration step further comprises administering said emulsion topically. 
     
     
       15. The method of claim 13 wherein said administration step further comprises administering said emulsion by means of a porous pad. 
     
     
       16. The method of claim 13 wherein said organic phosphate-based solvent comprises a trialkyl phosphate. 
     
     
       17. The method of claim 13 wherein said carrier oil consists essentially of a vegetable oil. 
     
     
       18. The method of claim 17 wherein said vegetable oil is soybean oil. 
     
     
       19. The method of claim 13, wherein the virus is selected from the group consisting of Herpesviridae, Togaviridae, Flaviviridae, Coronaviridae, Rhabdoviridae, Filoviridae, Paramyxoviridae, Orthomyxoviridae, Arenaviridae, Retroviridae, and Hepadnavirida. 
     
     
       20. The method of claim 13, wherein the virus is HIV. 
     
     
       21. The method of claim 13, wherein the virus is selected from the group consisting of HSV-1, HSV-2, CMV and VSV. 
     
     
       22. The method of claim 13, wherein said virus inactivating emulsion is non-toxic to the affected subject. 
     
     
       23. The method of claim 13, wherein said virus inactivating emulsion is not irritating to the affected subject. 
     
     
       24. The composition of claim 8, wherein each alkyl group of said solvent has one to ten carbon atoms. 
     
     
       25. The method of claim 13, wherein said emulsion is administered to said subject oropharyngeally, orally, venereally, or rectally. 
     
     
       26. A non-toxic composition for inactivating an envelope virus on the surface of a substrate, said composition comprising a storage stable, virus inactivating, oil-in-water emulsion composed of droplets having a mean particle size in the range of about 0.5 to 1.5 microns in the form of an oil phase distributed in an aqueous phase with a non-ionic stabilizer selected from the group consisting of Tween 20, Tween 80 and Triton X-100, said nonionic stabilizer being present in between about 0.2-2% of said composition, said oil phase containing a carrier oil and tributyl phosphate, said tributyl phosphate forming about 0.2-2% of said composition. 
     
     
       27. A method of inactivating an envelope virus on the surface of a substrate comprising the steps of: providing a non-toxic composition comprising a storage stable, virus inactivating, oil-in-water emulsion composed of droplets having a mean particle size in the range of about 0.5 to 1.5 microns in the form of an oil phase distributed in an aqueous phase with a non-ionic stabilizer selected from the group consisting of Tween 20, Tween 80 and Triton X-100, said nonionic stabilizer being present in between about 0.2-2% of said composition, said oil phase containing a carrier oil and and tributyl phosphate, said tributyl phosphate forming about 0.2-2% of said composition; and   contacting said envelope virus with said emulsion such that said virus is inactivated.   
     
     
       28. The method of claim 27, wherein said substrate is in contact with a human or animal subject. 
     
     
       29. The method of claim 27, wherein said substrate is the skin of a human or animal subject.